The midline vestibulo-cerebellum, consisting of the nodulus (vermis lobule X) and uvula (vermis lobule IX), has been long implicated in spatial orientation and visual-vestibular interactions but little is known about the underlying neurophysiology. The long-term goal of these studies is to understand the cerebellar processing of vestibular information and subcortical visual/vestibular interactions. The proposed aims are motivated by a model of inertial motion detection and recent findings that nodulus/uvula Purkinje cells reflect the necessary canal/otolith interactions that are necessary to separate net gravitoinertial acceleration into gravitational and translational components. Here we propose to further probe the signal processing between the vestibular nuclei, the cerebellar nuclei and the nodulus/uvula and to explore the properties of nodulus/uvula Purkinje cells and their connectivity with the vestibular and fastigial nuclei. We hypothesize: (i) that inertial vestibular motion signals from canal/otolith convergence are computed within the nodulus/uvula cortical circuitry and its interconnections with the vestibular/cerebellar nuclei;(ii) that these same areas also implement the visual/vestibular convergence necessary for distinguishing tilt and translation at low frequencies;and (iii) that complex spike activity of Purkinje cells carry visual translation signals needed for system calibration. In addition, we will address the functional relevance of the rostral fastigial nuclei during both reflexive eye movements and a self-motion direction discrimination task. To address these aims and hypotheses, we propose a multi-faceted approach using multiple techniques, including single unit recording, orthodromic/antidromic identification of physiologically-characterized neurons, behavioral analysis and chemical inactivation. Together, these studies will provide a vital test of the hypothesis that NU and NU-target neurons in the vestibular and cerebellar nuclei represent the main conduit of inertial multisensory processing for self-motion perception and spatial orientation. Such signals are vital for allocentric orientation and inertial navigation. Results and conclusions would be important in understanding spatial orientation deficits that typically accompany NU lesions. They will also provide the first evidence for or against a direct link between subcortical neural activities and perception and will bridge the gap between traditional vestibular system analysis and modern, functionally-relevant, correlation analysis techniques relating neural activities with animal's behavioral choices. PUBLIC HEALTH RELEVANCE: The vestibulo-cerebellum in the posterior vermis and its interconnections with brainstem nuclei are vital for spatial orientation and motion detection. Clinical and experimental lesions involving these areas lead to clinical nystagmus and reduced visual acuity, postural instability and loss of spatial orientation. Neurological correlates of central vestibular disorders are still a mystery, posing a major hurdle in defining effective therapeutic strategies. The experiments proposed here aim at filling a very notable gap in knowledge, important for understanding and treating both basic postural and reflexive deficits as well as cognitive deficits of spatial perception.